Let’s talk about a potential new high-tech mine in Minnesota, how scientists have created a synthetic mouse embryo using stem cells, and a major breakthrough in the cause of and treatment for Down Syndrome.
Let’s talk about a potential new high-tech mine in Minnesota, how scientists have created a synthetic mouse embryo using stem cells, and a major breakthrough in the cause of and treatment for Down Syndrome.
Remote Mines
Mouse Embryos
Down Syndrome Treatment
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Find episode transcripts here: https://curiosity-daily-4e53644e.simplecast.com/episodes/remote-mines-mouse-embryos-down-syndrome-treatment
[SFX: INTRO MUSIC/WHOOSH]
NATE: Hi! You’re about to get smarter in just a few minutes with Curiosity Daily from Discovery. Time flies when you’re learnin’ super cool stuff. I’m Nate.
CALLI: And I’m Calli. If you’re dropping in for the first time, welcome to Curiosity, where we aim to blow your mind by helping you to grow your mind. If you’re a loyal listener, welcome back!
NATE: Today you’ll learn about a potential new high-tech mine in Minnesota, how scientists have created a synthetic mouse embryo using stem cells, and we’ll explore a major breakthrough in the cause of and treatment for down syndrome.
CALLI: Without further ado, let’s satisfy some curiosity!
[SFX: WHOOSH]
CALLI: Nate, I know we’re pretty excited about the shift from gas cars to electric cars, but did you know one of the biggest challenges is getting the necessary materials to make the batteries?
NATE: I’ve heard some things about that, isn’t it stuff like nickel and cobalt?
CALLI: Exactly. We only have one active nickel mine in the US. But recently, a mining company has proposed building a high-tech mine in rural Minnesota to meet the growing need for the metal used in US electric car batteries.
NATE: I didn’t even realize we had nickel in Minnesota, I thought we sourced it from the other side of the world?
CALLI: Well, you’re right. Right now we rely on Indonesia and the Philippines for most of it. But Minnesota actually has a lot of nickel, copper, and cobalt, as the result of a 1.1 billion year-old volcanic eruption. The U.S. does already have one nickel mine in Michigan, but experts say its resources will be depleted by 2026. By having another domestic mine, the supply chain will all be internal and make sure the materials aren’t traveling all over the world before being manufactured stateside.
NATE: I’m still stuck on a volcano in Minnesota! So what would this kind of mine look like?
CALLI: Well, the company proposing the mine says it will be a high tech operation. They’re currently working to make a 3D model of underground sulfide ore deposits so they can go in and target them specifically without messing up too much of other nearby land. It’s kinda like picking your favorite color M&M from a bowl without disturbing the other ones. Sulfide ore can be pretty messy stuff, so they’re also promising to store any toxic by-products and mine deep in the bedrock to avoid groundwater. These factors are definitely concerning the local community, though, and there’s been a lot of backlash.
NATE: Alright, well that doesn’t sound so bad, plus I’m sure it’d bring some jobs to the area. So what kind of concerns do the locals have?
CALLI: Well, the mine is causing some controversy in the area for fear of environmental impacts. And those concerns are fair because there isn’t a mine anywhere in the world that hasn’t had any environmental impacts. Sulfide ore mines have a…horrible track record. Talon Metals, the company proposing the mine, is promising to contain the byproducts, but that is waaaay easier said than done. These kinds of mines often leak sulfuric acid and heavy metals that can spoil lakes and streams, and many of the waterways in the area feed into the Mississippi.
NATE: Oh man I can’t imagine what cleaning something like that would take.
CALLI: It's a huge undertaking, many old copper mines in the US are now superfund sites! A superfund is a program that cleans up sites that are contaminated with hazardous substances. What’s more, members of the indigenous Ojibwe tribes live just about a mile from the proposed mine site, and they’ve been collecting wild rice in the area for far longer than anyone has been thinking about mining it.
NATE: Ok that is not good, is the metal company working with the tribe?
CALLI: They’ve had a lot of meetings with members and representatives, but a lot of members of the tribe are concerned by the risks, and this mine is in one of the poorest parts of Minnesota, which means the local people who would take the risks, wouldn’t even be able to afford the cars the metals go to.
NATE: Ok, maybe this is a silly question, but if we already have mines in other places in the world, why would we want to wade into the mess and risk of this kind of mining here in the US?
CALLI: Sure, it’d be nice not to have to deal with it. But, a lot of those mines we rely on don't take the same environmental precautions we do here in the US, they leach chemicals, clear cut rainforests for strip mining, and burn coal to process the metals. So it's hard to feel like we are helping the environment by using them in eclectic cars. Plus our demand for electric cars in the US is going to increase six fold by 2030!
NATE: Okay, that is a tough problem…I don’t even know what we are supposed to do here. Are there other uninhabited areas we could mine in?
CALLI: Much of our domestic supply of these materials is near tribal land. It really just points out how hard our transition to a greener world, a transition we have to make, is going to be. We’re sure to face new challenges all the time. Right now, Talon Metals is starting the environmental review process, and they hope to have the 400 million dollar mine opened by 2026.
NATE: Alright, what about those concerns from the tribes!
CALLI: Well, Talon keeps talking and working with the tribal leaders, but at some point it might come down to faith and hope that nothing goes wrong.
NATE: Ah, I want these future technologies so badly I just hope we can get there without environmental damage.
CALLI: In the meantime we just have to watch and see how successful these new high-tech safety measures are, and hope for the best.
[SFX: WHOOSH]
NATE: Asexual reproduction, the ability to give birth without sexual intercourse, is really interesting to me. You usually see it in things like starfish or insects. So, when I discovered a new study where scientists created MOUSE embryos out of stem cells, I was pretty excited.
CALLI: WHOA. So they created actual living, breathing tissue from scratch???
NATE: Well, that’s the crazy part: the embryos are “synthetic,” meaning that they were created artificially in a lab but they have identical features to a natural eight and a half day old embryo, and have the same cellular structures… and even have beating hearts.
CALLI: Fascinating stuff. What’s the goal of something like this?
NATE: In the short term, they believe this can be used to better understand the early stages of development, as well as study any and all mechanisms behind disease without the need for lab animals. Plus, we may also be able to create synthetic human embryos for research in the future.
CALLI: That’s actually a lot of potential for a lot of good things, but it’s also giving me a bit of a sinister feeling. I don’t love the idea of synthetic fetuses in a lab. What even inspired them to do this?
NATE: Well, building embryo models is an alternative way to study issues like early-stage pregnancy loss and problems with in-vitro fertilization. For example, embryos created for IVF fail to implant or develop in around 70% of cases. These models can help us explore why that is in a safe and, frankly, cost-effective way.
CALLI: Ok, I guess I can see the benefits. How are the embryos made exactly?
NATE: First, researchers combine embryonic stem cells with two other types of stem cells from mice in a lab. At first, the embyroids as they call them weren’t perfect, but eventually, the best ones they created were indistinguishable from natural mouse embryos. And it wasn’t just the heart that developed, either… some had structures resembling HEADS.
CALLI: That’s some real Doctor Frankenstein energy, Nate. Sounds a little scary but also… a little cool? Is there anything else like this out there?
NATE: Not really. This is the first model that would allow us to study brain development head on, in the context of developing a mouse embryo at least. It wasn’t easy to get there, either - the researchers leading the charge have been working on this for decades, and didn’t even submit their work until November 2021.
CALLI: That’s a long time to work on one project. What’s the next step for this experiment?
NATE: Older embryos. They want to develop embryos that are older than eight and a half days, and eventually get them to term. For a mouse, that’s twenty days old. Unfortunately, getting the mouse past eight and a half days has been very tough. And even if they manage to get the embryo to eleven days of development, they believe it will fail without a placenta… so, the next move would be creating a synthetic placenta.
CALLI: Woof. That sounds like a lot of work. So we shouldn’t hold our breaths for the human version of this anytime soon, right?
NATE: Well, researchers say it’s “the next obvious thing,” but also caution us to… well, yeah, not hold our breaths. However: other scientists have already used human stem cells to create a “blastoid,” which is a structure mimicking a pre-embryo. That would serve as a research alternative to a real one.
CALLI: So how do people feel about the ethics of all this?
NATE: Well, it’s complicated. For many years, there was a “14-day-rule” on growing human embryos in a lab. But last year, the International Society for Stem Cell Research recommended relaxing the rule under limited circumstances. I should make it clear that most scientists stress that growing a baby from a synthetic human embryo is not only not possible, it’s not even under consideration.
CALLI: Huh. So what’s the point, then?
NATE: The point is that similar experiments to the mouse embryo will be done with human cells and that, at some point, will have us stop to consider the implications of how far this experiment can even go. This research could potentially save lives, pregnancies, and even reduce pain in vitro. But the further it goes, the further the ethical quandaries are raised.
CALLI: Mm. So this really is like Frankenstein: are we playing good doctor, or are we playing God?
NATE: Exactly.
[SFX: WHOOSH]
CALLI: People who live with Down syndrome face a lifetime of uncertainty, Nate. They live with sensory, reproductive, and intellectual symptoms that can worsen with age. But a new study out of France has discovered that many of these symptoms are being worsened by one hormone - specifically, a lack of that hormone.
NATE: It’s interesting to me that Down syndrome is something we’ve known about since the 1800s, but still understand very little in comparison to other conditions.
CALLI: That’s right. And since it strikes as many as 1 in 700 births, you think knowing more about it would be a higher priority. Which is where the good people at Lille University in France come in. They’ve discovered that there’s a hormone called GnRH that’s lacking in those with Down syndrome. And by restoring that hormone, we see a HUGE increase in cognitive performance.
NATE: That’s fascinating. I’m guessing the deficiency starts at birth?
CALLI: Amazingly, no! Children with Down syndrome actually have cognitive abilities on par with their peers until puberty when the decline occurs. It was also already known by the researchers that the chromosome affected by Down syndrome included genes that had negative effects on GnRh neurons after birth. Taking that together, the researchers decided to see if there was a link between GnRH levels and cognitive decline. Thus - the study.
NATE: So how did they do the study?
CALLI: They ran a series of cognitive tests on both prepubescent and young adult mice that had a genetic anomaly in line with humans with Down syndrome. What they found was that the mice’s cognitive conditions were pretty much identical to human counterparts: until puberty, the mice could tell if they were encountering a familiar or unfamiliar object. After puberty, though? Nothing.
NATE: Fascinating.
CALLI: Right? And listen to this: they looked into brain tissue samples from the mice at different ages to see if a gradual GnRH decrease was linked, and over time, there was in fact a GnRH decrease occurring.
NATE: Wow, okay. So you said earlier that restoring GnRH is possible, too. Does that mean that the cognitive abilities of the mice improved?
CALLI: Yes, but it wasn’t easy to figure out. So they pulled in a professor from the University of Lausanne, who specialized in GnRH injections that mimics natural hormone production. They used this method to treat the mice and discovered… a restoration of cognitive abilities in both male and female mice.
NATE: That’s so amazing, Calli. When can they test this on humans?
CALLI: That’s the best part: they already have. The team put together a small pilot study of seven men with Down syndrome, aged 20 to 50 years old, each with intellectual disabilities. After they went through cognitive testing and MRI scans, they were fitted with special pumps that let out a small dose of GnRH every two hours for six months.
NATE: And what were the results?
CALLI: Something happened that exceeded even their most conservative estimates: six of the patients showed cognitive improvements of anywhere from 20 to 30%. What do I mean by that? They were able to understand instructions more efficiently. Improved reasoning abilities. Better memory and greater attention. It was a resounding success, and even more surprising was that their brain connectivity was shown through an MRI to have changed, too.
NATE: I wasn’t expecting this at all, Calli. This is huge. Are you saying that a cure for Down syndrome has been developed?
CALLI: No, I wouldn't say it that way at all. Down syndrome isn’t something that needs to be cured, Nate. It’s a neuro-divergent condition and not a problem that needs to be fixed. It’s more the deficiency of the hormone that needs treatment, and if caught at an early enough age, can save people with Down syndrome from a harder existence than they need or deserve. This isn’t a cure for Down syndrome - this is a treatment for pain.
NATE: Okay, yeah that makes sense. So what’s next?
CALLI: There’s still a lot of research that needs to be done before GnRH therapy can be used as an actual treatment. The researchers are in the process now of launching a randomized, multicenter study out of Switzerland with 60 or 70 patients, and this time, the focus will be predominantly on women with Down syndrome to see if sex plays a factor in the treatment.
NATE: Wonderful. Here’s hoping that the study works out!
[SFX: WHOOSH]
NATE: Let’s recap what we learned today to wrap up.
CALLI: As US demand for electric cars increases, so does demand for the materials that go into making the batteries. Mining those materials is messy work though, and puts a lot of vulnerable land, and people, at risk.
NATE: Stem cell research has led to the creation of an innovative synthetic mouse embryo, complete with a working artificial heart. Eventual expansion of this research could lead to innovations for human embryos as well, but scientists caution those conducting such research to consider the ethical boundaries of how far research like this should go!
CALLI: For decades, the causes of Down syndrome have eluded scientists, but a recent breakthrough study has found a cause and potential treatment for the condition. A hormone deficiency is the culprit in cognitive decline among adults with Down syndrome, and a groundbreaking new therapy can help reverse that decline. In due time, this therapy could be a way to ensure people with Down syndrome live longer, happier, and healthier lives than they already do!